The goal of this research is to investigate this spatial/temporal relationship between cerebral hemodynamics, neuronal functional and headache pain in patients with migraine using functional magnetic resonance imaging (fMRI). Migraine, with or without antecedent aura, is a major cause of morbidity; afflicting over 17% of women and 6% of men in the United States. Although migraine is well characterized clinically, pathophysiologically it remains an enigma. Traditionally, it has been assumed that aura symptoms arise from focal ischemia due to transient vasoconstriction of cerebral vessels and that the headache phase reflects stretching of vessel walls engorged after a compensatory vasodilation. More recent data has called several of these assumptions into question. To address these issues, we have (1) optimized fMRI techniques to rapidly measure relative cerebral blood flow (rCBF), cerebral blood volume (rCBV), mean transit time (MTT), permeability of the blood-brain barrier (pBBB) and diffusion over time noninvasively, and (20 recruited migraineurs who work close by the MRI site and are available for ictal imaging within minutes of the onset of symptoms. We have demonstrated that patients can be imaged with these techniques during spontaneous migraine aura and headache. Our preliminary fMRI data suggest that both neuronal function and cerebral hemodynamics are initially abnormal in migraine aura, with persistence of some findings well into the headache period. New studies proposed here will be used to detect the presence of cerebral ischemia, investigate micro- and microvascular CBV changes, and search for possible "generator" sites for migraine pain. Our data will also allow us to directly quantify the presence and rate of cortical spreading depression, and measure regional vasodilatation and its relationship to possible increased vascular permeability. These fMRI data will be used to test several specific hypotheses on the role of hemodynamic perturbations on the causes and sequella of migraine. The long term goal of this research is to provide fundamental insight into the pathophysiology of migraine, allowing for improved treatment strategies.